HealthyPhase 2NCT00006070
Etanercept (Enbrel) to Treat Pain and Swelling After Third Molar Extraction
A Phase 2 study testing etanercept (Enbrel) in people with Healthy and Inflammation, run by National Institute of Dental and Craniofacial Research (NIDCR) at 1 site in United States.
Trial summary
This study will evaluate the effects of the anti-inflammatory drug etanercept (Enbrel) on relieving pain and swelling after oral surgery. The Food and Drug Administration has approved Enbrel for treating symptoms of rheumatoid arthritis, including pain. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Healthy, Inflammation
- What is being tested?
- etanercept (Enbrel)
- How many people
- 86 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2000to May 2004
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female volunteers referred for extraction of third molars willing to undergo two surgical appointments for the extraction of unilateral third molars.
- Between the ages of 16 to 35 years (based upon eruption patterns and age-related complications associated with surgical extraction of third molars).
- In good general health - ASA status 1 or 2 (healthy subjects based upon criteria for safe outpatient conscious sedation).
- Willing to undergo observation period for four hours postoperatively.
- Willing to return at 48 hours for measurement of pain, swelling, and tissue biopsy.
- Willing to return for a total of four visits beyond the screening visit.
Who cannot join
- Pregnant or lactating females.
- Current mental disorder or substance abuse.
- Allergy to aspirin or NSAIDs.
- Chronic use of medications confounding assessment of the inflammatory response or analgesia (antihistamines, NSAIDs, steroids, antidepressants).
- Presence of chronic debilitating disease (such as diabetes, rheumatoid arthritis, liver disease, etc).
- Presence of symptomatic tooth suggesting infection or inflammation.
- Unusual surgical difficulty encountered during the surgical procedure.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Dental And Craniofacial Research (NIDCR)
Bethesda, Maryland, 20892
About this study
Official title: Safety and Efficacy of a TNF Receptor Fusion Protein for Injury-Induced Inflammation and Sequelae
This study will evaluate the effects of the anti-inflammatory drug etanercept (Enbrel) on relieving pain and swelling after oral surgery. The Food and Drug Administration has approved Enbrel for treating symptoms of rheumatoid arthritis, including pain.
Healthy volunteers 16 to 35 years of age who require third molar (wisdom teeth) extractions may be eligible for this study. Participants must not be allergic to aspirin or to non-steroidal anti-inflammatory drugs (NSAIDs). Candidates will be screened for eligibility with a medical history and oral examination, including X-rays if needed.
Read more
Participation in the study requires four clinic visits: two for surgery and two for follow-up:
Visit 1:
Patients will have ultrasound pictures taken to measure cheek size. One hour before surgery, they will receive a dose of either 25 milligrams (mg) of Enbrel; 15 mg of the standard pain medicine Toradol; or a placebo (salt-water) through an arm vein. A local injection of an anesthetic (lidocaine) will be given before surgery to numb the mouth, and a sedative (Versed) will be infused through a vein to induce sleepiness. When the anesthetic takes effect, a small piece of tissue will be removed from the inside of the cheek, and then the upper and lower molars on one side of the mouth will be extracted. After surgery, a small piece of tubing will be placed in the lower extraction site, from which samples will be collected to measure chemicals involved in pain and inflammation. Patients will stay in the clinic for 4 hours after surgery while the anesthetic wears off and will complete pain questionnaires during that time. If, an hour after surgery, patients have pain that is not relieved by the treatment given before surgery, they may receive acetaminophen (Tylenol) and codeine for pain. Another biopsy will be taken (under local anesthetic) from the inside of the cheek when pain occurs or at the end of the 4-hour observation period. The tubing then will be removed and the patient discharged with Tylenol and codeine for pain.
Visit 2:
Patients will return to the clinic in the morning 48 hours after the oral surgery for a 1- to 2-hour visit. They will fill out questionnaires, undergo ultrasound imaging of both cheeks and have another biopsy taken from the inside of the cheek on the operated side.
Visits 3 and 4:
Three weeks after the first surgery patients will schedule extraction of the two wisdom teeth on the other side of the mouth, and the procedures for visits 1 and 2 will be repeated.
Read the detailed description
The proposed investigation is a randomized, double-blind, placebo and positive-controlled within-subjects design clinical study to evaluate the role of the cytokine tumor necrosis factor (TNF) in acute inflammation using a specific TNF receptor antagonist, etanercept (Enbrel, Immunex Corporation, Seattle, WA). The goal of this study is to determine whether inhibition of TNF bioactivity can attenuate acute inflammation. The anti-inflammatory and adverse effects of etanercept, a recombinant TNF receptor fusion protein, will be evaluated using a model of tissue injury, the oral surgery model. Briefly, healthy volunteers referred for third molar extraction will undergo the surgical extraction of third molars with local anesthesia and conscious sedation. At the completion of the surgical procedure, a microdialysis probe will be placed under the mucogingival flap previously elevated for the surgical procedure and subjects will be observed for pain and swelling over the course of four hours following surgery. Tissue biopsies prior to and following surgery will be obtained from the buccal mucosa. Etanercept or control will be administered parenterally one hour prior to surgery. Tissue levels of pro-inflammatory cytokines, growth factors, and inflammatory mediators will be measured at time intervals postoperatively. Pain and swelling will be assessed postoperatively over the course of four hours and at 48 hours. Demonstration of amelioration of pain, swelling, and/or changes in levels of tissue mediators will be taken as evidence of an acute anti-inflammatory effect of etanercept. Since the fusion protein (hereafter, TNFR:fc) specifically binds TNF-alpha and prevents its interaction with cellular receptors, changes in the inflammatory cascade and clinical endpoints of inflammation may provide insight into role of TNF-alpha in the pathophysiology of acute inflammation and its clinical sequela.
- Conditions
- Healthy, Inflammation
- Being tested
- etanercept (Enbrel)
- Keywords
- Oral Surgery, Swelling, Pain, TNF, Etanercept
- Medical subject headings
- Inflammation, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
etanercept (Enbrel)Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2000 (estimated)
- Study startJul 2000
- Study completionMay 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 86 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Dental and Craniofacial Research (NIDCR)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00006070
- Sponsor's protocol ID
- 000168
- Other IDs
- 00-D-0168
- Status last verified
- May 2004
- First submitted
- 18 Jul 2000
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Mohler KM, Torrance DS, Smith CA, Goodwin RG, Stremler KE, Fung VP, Madani H, Widmer MB. Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol. 1993 Aug 1;151(3):1548-61.
PubMed 8393046Fisher CJ Jr, Agosti JM, Opal SM, Lowry SF, Balk RA, Sadoff JC, Abraham E, Schein RM, Benjamin E. Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. The Soluble TNF Receptor Sepsis Study Group. N Engl J Med. 1996 Jun 27;334(26):1697-702. doi: 10.1056/NEJM199606273342603.
PubMed 8637514Chen L, Salafranca MN, Mehta JL. Cyclooxygenase inhibition decreases nitric oxide synthase activity in human platelets. Am J Physiol. 1997 Oct;273(4):H1854-9. doi: 10.1152/ajpheart.1997.273.4.H1854.
PubMed 9362253
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of a TNF Receptor Fusion Protein for Injury-Induced Inflammation and Sequelae
- ClinicalTrials.gov ID
- NCT00006070
- Acronym / sponsor ID
- 000168
- Conditions
- Healthy, Inflammation
- Keywords
- Oral Surgery, Swelling, Pain, TNF, Etanercept
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants
- Lead sponsor
- National Institute of Dental and Craniofacial Research (NIDCR)US National Institutes of Health
- Study start
- Jul 2000
- Study completion
- May 2004
- First posted
- 19 Jul 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the effects of the anti-inflammatory drug etanercept (Enbrel) on relieving pain and swelling after oral surgery. The Food and Drug Administration has approved Enbrel for treating symptoms of rheumatoid arthritis, including pain.
Healthy volunteers 16 to 35 years of age who require third molar (wisdom teeth) extractions may be eligible for this study. Participants must not be allergic to aspirin or to non-steroidal anti-inflammatory drugs (NSAIDs). Candidates will be screened for eligibility with a medical history and oral examination, including X-rays if needed.
Participation in the study requires four clinic visits: two for surgery and two for follow-up:
Visit 1:
Patients will have ultrasound pictures taken to measure cheek size. One hour before surgery, they will receive a dose of either 25 milligrams (mg) of Enbrel; 15 mg of the standard pain medicine Toradol; or a placebo (salt-water) through an arm vein. A local injection of an anesthetic (lidocaine) will be given before surgery to numb the mouth, and a sedative (Versed) will be infused through a vein to induce sleepiness. When the anesthetic takes effect, a small piece of tissue will be removed from the inside of the cheek, and then the upper and lower molars on one side of the mouth will be extracted. After surgery, a small piece of tubing will be placed in the lower extraction site, from which samples will be collected to measure chemicals involved in pain and inflammation. Patients will stay in the clinic for 4 hours after surgery while the anesthetic wears off and will complete pain questionnaires during that time. If, an hour after surgery, patients have pain that is not relieved by the treatment given before surgery, they may receive acetaminophen (Tylenol) and codeine for pain. Another biopsy will be taken (under local anesthetic) from the inside of the cheek when pain occurs or at the end of the 4-hour observation period. The tubing then will be removed and the patient discharged with Tylenol and codeine for pain.
Visit 2:
Patients will return to the clinic in the morning 48 hours after the oral surgery for a 1- to 2-hour visit. They will fill out questionnaires, undergo ultrasound imaging of both cheeks and have another biopsy taken from the inside of the cheek on the operated side.
Visits 3 and 4:
Three weeks after the first surgery patients will schedule extraction of the two wisdom teeth on the other side of the mouth, and the procedures for visits 1 and 2 will be repeated.
Detailed description
The proposed investigation is a randomized, double-blind, placebo and positive-controlled within-subjects design clinical study to evaluate the role of the cytokine tumor necrosis factor (TNF) in acute inflammation using a specific TNF receptor antagonist, etanercept (Enbrel, Immunex Corporation, Seattle, WA). The goal of this study is to determine whether inhibition of TNF bioactivity can attenuate acute inflammation. The anti-inflammatory and adverse effects of etanercept, a recombinant TNF receptor fusion protein, will be evaluated using a model of tissue injury, the oral surgery model. Briefly, healthy volunteers referred for third molar extraction will undergo the surgical extraction of third molars with local anesthesia and conscious sedation. At the completion of the surgical procedure, a microdialysis probe will be placed under the mucogingival flap previously elevated for the surgical procedure and subjects will be observed for pain and swelling over the course of four hours following surgery. Tissue biopsies prior to and following surgery will be obtained from the buccal mucosa. Etanercept or control will be administered parenterally one hour prior to surgery. Tissue levels of pro-inflammatory cytokines, growth factors, and inflammatory mediators will be measured at time intervals postoperatively. Pain and swelling will be assessed postoperatively over the course of four hours and at 48 hours. Demonstration of amelioration of pain, swelling, and/or changes in levels of tissue mediators will be taken as evidence of an acute anti-inflammatory effect of etanercept. Since the fusion protein (hereafter, TNFR:fc) specifically binds TNF-alpha and prevents its interaction with cellular receptors, changes in the inflammatory cascade and clinical endpoints of inflammation may provide insight into role of TNF-alpha in the pathophysiology of acute inflammation and its clinical sequela.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female volunteers referred for extraction of third molars willing to undergo two surgical appointments for the extraction of unilateral third molars.
- Between the ages of 16 to 35 years (based upon eruption patterns and age-related complications associated with surgical extraction of third molars).
- In good general health - ASA status 1 or 2 (healthy subjects based upon criteria for safe outpatient conscious sedation).
- Willing to undergo observation period for four hours postoperatively.
- Willing to return at 48 hours for measurement of pain, swelling, and tissue biopsy.
Key exclusion criteria (7 listed)
- Pregnant or lactating females.
- Current mental disorder or substance abuse.
- Allergy to aspirin or NSAIDs.
- Chronic use of medications confounding assessment of the inflammatory response or analgesia (antihistamines, NSAIDs, steroids, antidepressants).
- Presence of chronic debilitating disease (such as diabetes, rheumatoid arthritis, liver disease, etc).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| etanercept (Enbrel) | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 8393046Mohler KM, Torrance DS, Smith CA, Goodwin RG, Stremler KE, Fung VP, Madani H, Widmer MB. Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol. 1993 Aug 1;151(3):1548-61.
- Background: PubMed 8637514Fisher CJ Jr, Agosti JM, Opal SM, Lowry SF, Balk RA, Sadoff JC, Abraham E, Schein RM, Benjamin E. Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. The Soluble TNF Receptor Sepsis Study Group. N Engl J Med. 1996 Jun 27;334(26):1697-702. doi: 10.1056/NEJM199606273342603.
- Background: PubMed 9362253Chen L, Salafranca MN, Mehta JL. Cyclooxygenase inhibition decreases nitric oxide synthase activity in human platelets. Am J Physiol. 1997 Oct;273(4):H1854-9. doi: 10.1152/ajpheart.1997.273.4.H1854.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing etanercept (Enbrel) in people with Healthy and Inflammation, run by National Institute of Dental and Craniofacial Research (NIDCR) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00006070, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.